Posted
by
kdawson
on Thursday November 01, 2007 @10:18AM
from the like-a-soprano-with-crystal dept.

wattrlz writes "In a development reminiscent of nineteenth century pseudo-science, the father-son team of Kong Thon and Shaw Wei Tsen recently demonstrated that the tobacco mosaic virus can be destroyed in vitro by nano-scale mechanical resonant vibrations induced by repeated ultra-short pulses from a laser. The total energy required is reportedly far below the threshold for human tissue damage and the technique should generalize to human pathogens. Cleaning stored blood is one obvious application."

The virus-deactivating laser works on a principle called forced resonance. The scientists tune the laser to the same frequency the virus vibrates on. Then they crank up the volume. Like a high-pitched sound shattering glass, the laser vibrates the virus until it breaks.

There was a Batman TV series episode where the bad guy was using sub/supersonic tones to resonate with various objects to destroy them. The plotline was that he was threatening to destroy whole buildings with his sonic blaster, and only Batman could save Gotham, but Batman himself was susceptible to the sonic blaster! Tune in next week, true believers!

This is also like the soprano opera singer who shatters glass with her voice. Only with lasers.

"This technique will be very useful to disinfect all the viruses, known or unknown," Tsen said. "This will make blood transfusion very safe."

Do you see the BS? They say here: UNKNOWN. Lets suppose, you can calibrate the laser against a known virus without harming human cells/tissue/whatever. How do you calibrate this magic laser to several unknown viruses at the same time?

I interpreted "known or unknown" to mean the known or unknown presence of a known virus. For example, maybe it's known that this blood donor had AIDS. So they blast the bag with AIDS-killing frickin laser beams.
All well and good, but suppose they don't know what other viruses are present? Maybe the donor had the flu? Maybe the donor had HPV? Rather than spending the money to test and run down any number of viruses that may be present in the blood just zap the baggie for AIDS, zap it again for influen

1. All proteins in your body, and all proteins your body can possibly assemble for a virus capsid (and it must, because that's how virii multiply) are made of the same 20 aminoacids. The result, however, can range from relatively simple enzymes to gigantic mollecules, and they're folded in lots of funny ways too, to work like they're supposed to.

I.e., I wouldn't be _too_ surprised if for _some_ particular frequencies (i.e., some very narrowly defined types of virii), something else in your cells had a resonance on the same frequency. Even if the total power isn't enough to vapourize a cell, it could still be pretty deadly.

2. A capsid isn't a monolythic thing, it's made of several proteins which assemble themselves in that shape. That's how your body produces more capsids for the viruses an infected cell manufactures. It produces the capsid pieces, and those then assemble themselves around the pieces of viral DNA or RNA that were copied too.

So I'm curious exactly in what way are the capsids "shattered" by that resonance. If it shatters the proteins themselves into aminoacids, yeah, that's the end of it. But then, see point 1, I'd worry which other proteins it can destroy like that. If it just shatters the (relatively) weaker bonds between the individual proteins that make the capsid, I would imagine that at least some of them will simply reassemble. Remember they're proteins which are pretty much built to do just that: connect to each other and form a capsid.

3. Their claim that it can shatter HIV virii, while leaving the T cells intact, seems somewhat missing the point. It's the kind of solution that a physicist would imagine, if he doesn't know much about how a virus works.

So let's get a bit into (a very over-simplified summary of) how a cell works, and a virus multiplies. (Warning: it's still a long read.)

Your cells are basically a chemical computer whose function include building more building blocks for itself, or for more copies of itself. Your proteins, for example, are encoded by your DNA, as triplets of nucleotides. One such triplet is a "codon", and it identifies one aminoacid. (With some redundancy. You use 20 aminoacids, but since there are 4 possible nucleotides and there are 3 of them, there are 64 possible combinations. So it's quite usual that 2 or 3 different combinations mean the same aminoacid.)

When a cell needs more of a certain protein, it first copies a segment of DNA to RNA and lets it loose. Each Then a ribosome reads that just like a piece of tape, one codon (group of 3 nucleotids) at a time, and assembles a chain of aminoacids matching that sequence. For each codon, it adds the matching aminoacid to the chain, and moves one position further. One codon means STOP, and when it reached that, it lets go of the newly built protein and stops.

A virus works much the same. It builds more capsids, for example, by just letting loose a chain of RNA in your cell, which contains the information on how to build a capsid piece. (If it's a DNA based virus, it will first have to transcribe it to RNA, same as your cell does.) When enough of those capsid pieces have been built, they assemble themselves in a capsid around such a RNA chain.

At the same time, of course, the virus will also have to get your cell to transcribe the RNA piece. That, however, is just a sub-case of the previous paragraph. One of the proteins encoded by the virus, is the "RNA replicase". It's an enzyme which copies RNA strands. So the virus will let one piece of tape with that information loose inside your cell, the cell transcribes it to RNA replicase, which in turn starts copying RNA strands non-stop. Some will be surrounded by the capsid pieces to form new virii, but some will just keep getting interpreted by your ribosomes, so the cell keeps producing more capsid pieces and more RNA transcriptase.

To sum it up, an infected cell is, essentially, reprogrammed to keep producing viruses until it bursts. It's those pieces of gene

Since all the blood cells are removed from the donated plasma, it'd be much easier to make sure there was zero effect on what is left (normal blood proteins), and there wouldn't be any cells to make new virus.

The laser shattered the capsid at low energy: 40 times lower, in fact, than the energy level that harmed human T-cells. Other types of radiation, like ultraviolet light, kill microbes on produce, but would damage human cells.

It seems to me like they're explicitly planning to use it on something that _does_ have cells left, and more specifically also the infected T cells. (Which would then continue to produce virus copies anyway.)

Considering that viruses are essentially bundles of proteins, and this laser trashes the virus, how would the laser not trash proteins in cells potentially containing the viruses?

There is no possible frequency of light that could preferentially hit a virus and miss everything around it. For biomolecules and especially for whole conglomerations of biomolecules (say, a cell) you reach a saturation of states (or more correctly, pairs of states) across all frequencies (within a reasonable range.) In other words, conglomerations of biomolecules have spectra that are broad. So if the laser was going to be used to try and excite vibrational states in the virus and eventually cause dissociation and fragmentation, you would inevitably be doing the same to some of the material around it, again assuming that the virus was in a cell or surrounded by other biomolecules.

From listening to Dr. Tsen, it really does seem to work for free virions floating in solution - but once they unpackage themselves and infect a cell, it does nothing.

You do make me wonder if this isn't doing more harm to cells than Dr. Tsen is aware of (which, given his utter lack of biology background would not surprise me). This could easily disrupt ribosomes, or possibly nucleosomes and similarly sized structures without causing cell death (

Some dr at the turn of the last century said that he could destroy all pathogens with a, "beam device" tuned to their, "mortal oscillatory rates" or some such. Very simillar claim. He also said he could see virii under his microscope.

In the later part of Rife's career, Medical researchers thought they had pretty much beat communicable diseases with vaccines and antibiotics. I wouldn't be completely surprised if Rife was on to something but couldn't get funding or positive attention because vaccines and antibiotics were so successful and considered to be "the" answer.
The article about Rife in Wikipedia doesn't sound like what I think of when I hear "18th century Pseudoscience".

More likely, we have some psuedoscience and years later someone comes up with something similar to it, so in hindsight people think 'they were onto something'.Or he had a similiar odea, but no science to back it up. Forexample: Maybe he heard of an opera singer cracking a glass and thought 'Hey, we should be able to do that to viruses'. Of course no way to study it, no science to back it, tend to make it a psuedoscience.

He invented a microscope which seem to work on magic, since no one has been able to get

He invented a microscope which seem to work on magic, since no one has been able to get the results he claimed.Also, he claimed to created a beam the cured a particular cancer. Non repeatable.

I thought the "beam" had something to do with his microscope. The "Rife machines" (which are still sold today) are basically just electrical function generators, which you tune to a specific frequency which supposedly will destroy a particular pathogen, and then hold a couple of electrodes in your hands connected to t

Being as they are using the resonant frequency to destroy the virus, I imagine the differences in the mechanical structures between viruses and other surrounding material would isolate the applied force to the virus.
Disclaimer: This is no where near my field of study.

I must admit, when I first read the headline on this one I was baffled - I had no idea what it was. However, after reading the article, I have come to understand just what this means for the medical community. The article talks about using lasers to destroy harmful, and previously incurable, diseases from stored blood in our blood banks, including HIV. This is a tremendous step forward for the scientific and medical communities. Of course, they still have to test it, since it has only been used in a test-tu

I wonder how effective this could be in preventing the spread of AIDS in discos and Apple Computer expos where lasers are used all the time as pulsating visual cues matched to the throbbing bass beat of heavy house and Hi-NRG techno.On a more serious note, I remember that it was once mentioned in some Star Trek episode that the transporters performed a full scan for pathogens of all "beamed" people and items. This sounds almost like that, except for the actual transportation of particles from one place to a

HIV doesn't live long outside the body. Hence, trying to sterilize a disco with lasers would be a bit of a waste.If you want to get more details as to why, some viruses are composed of just the capsid, some, however, include a viral envelope: a membrane of a double layer of lipids, much like the membrane of your own cells. In fact, it _is_ a piece of the membrane of the infected cell that produced the copies of the virus, plus some viral proteins to help it attach to the next cell it infects.

Can this be tuned --or perhaps tuned with the assistance of another chemical marker-- to act as a "hunter killer" for auto-immune activated diseases such as multiple sclerosis, lupus, etc. where the resonant pulses would only kill the erroneously activated white blood cells and not the non-reactive white blood cells?

Because if so this becomes in effect a computerized vaccine against a wide variety of ailments that have no other good medicinal choices. And because computing power is still rising exponentially faster than just about any other form of tech, this could be a whole lot quicker to market.

Doubtful. They basically tune the pulse frequency to the resonant frequency of the virus's protein shell to break it. So it really needs to be tuned to a specific frequency to kill a specific thing. I would think white blood cells, activated or not, are too similar to be differentiated this way. Though I am no biologist, so correct if I am wrong - and I hope I am wrong because this would be an amazing breakthrough not just in autoimmune diseases but also cancer.

They are already working on an MS treatment where they basically take a person's own white blood cells and then modify them to go after the myelin-reactive white blood cells. Which means that they must have a way of identifying them -- so the question becomes, can a treatment be developed which basically attracts the myelin reactive cells only into the femtolaser scanning field where thay can be nuked, without killing off the rest of the immune system.

First, This will only work if the resonance breaks the bonds inside the proteins that create the subunits that self-assemble into the viral capsids. If the resonance only separates the weakly-bound subunits, then the resulting fragments will tend to re-self-assemble into whole viruses again. To use a bricks and mortar analogy -- if the device only breaks the mortar, the bricks can reused. The trick is to break the bricks.

Second, this solution requires a specific pulse frequency for each virus. It's not a broad-spectrum disinfectant. That suggests that viruses can easily evolve to defeat the device. Mutants that add a few non-functional amino acids to their capsid protein chains or that decorate the capsid surface with different biochemical groups would change the resonant frequency and allow mutants to escape and breed. One can even imagine evolution selecting for viruses that have inherent damping so that no resonant frequency can build enough energy to disrupt the shell. For example, a virus might become effectively heterozygous so that its shell is randomly constructed of two slightly different subunit sequences. A capsid that is not perfectly crystalline would lack a strong resonant frequency and escape disruption.

Overall, this looks like a very promising weapon in the on-going arms race against viruses.

Second, this solution requires a specific pulse frequency for each virus. It's not a broad-spectrum disinfectant. That suggests that viruses can easily evolve to defeat the device. Mutants that add a few non-functional amino acids to their capsid protein chains or that decorate the capsid surface with different biochemical groups would change the resonant frequency and allow mutants to escape and breed.

I had the same thought at first. However then I realized that we're really only worried about a few vi

So just put the frequencies that kill different viruses into a file and just have the laser cycle through them. The evolution problem could be solved by regularly updating your antivirus files. Naturally most people won't do this and will end up compelled to send junk mail to people...

First, This will only work if the resonance breaks the bonds inside the proteins that create the subunits that self-assemble into the viral capsids. If the resonance only separates the weakly-bound subunits, then the resulting fragments will tend to re-self-assemble into whole viruses again. To use a bricks and mortar analogy -- if the device only breaks the mortar, the bricks can reused. The trick is to break the bricks.

It sounds like it probably only breaks apart the subunits. However, once the virus is

A laser that disrupted covalent bonds in proteins would most certainly be detrimental to human cells too. There's nothing special about the covalent bonds of virus proteins over human proteins. What is special is the tertiary structure packing of coat proteins.
I'm also not convinced that the process will be completely reversible as you suggest. Monomer coat protein could very easily dilute into very low concentrations once the virus is disassembled by destabilizing the complexed state (i.e. the intact virus).
Nonetheless, I have concerns too. I would think that tissue penetration of the radiation would be quite poor. Tissue is more invisible to X-rays than lower frequency radiation. Presumably, this method uses lower frequency radiation -- I couldn't see it mentioned in the story. These pulses may break viruses down in solution, but getting it to deep tissue is another matter entirely.

Getting to deep tissue may not be a big problem. Aren't most virii found in the bloodstream? If so, and if this works out, couldn't you hook a patient to a dialysis-like machine where the blood leaves the body, is treated, and is readmitted? Then the patient sits around for an hour and bingo, no more AIDS.

Of course, I'm just a computer guy, we'd need an appropriate expert to say whether or not that's practical. And the laser treatment may not pan out anyway, but it sounds very cool.

This approach is a really clever way of eliminating specific viruses from a specific tissue or fluid. It's a shame that it would be darn hard to apply to an entire organism (to, for example, cure a viral infection) because you would have to illuminate the whole organism with the laser. It also has limited application in cleaning blood because it has to be tuned for a specific virus (i.e. AIDS) and would have run multiple times to remove others.

Yeah, it'd be interesting to see if some sort of dialysis-like device would be useful in some chronic viral diseases like AIDS... I guess it would depend on how long the viral particle stays viable in the blood, at what rate it is being replaced by infected cells, etc.

It also has limited application in cleaning blood because it has to be tuned for a specific virus (i.e. AIDS) and would have run multiple times to remove others.

You could pump the blood through several lasers in series; the lasers would be tuned to different frequencies. With this setup, the blood would be zapped many different ways but would make only one pass through the purifier. The process should be reasonably quick.

While the details aren't great in TFA, I can imagine dialysis-like machines getting setup to treat patients. What the article didn't really hit on was the total capacity the laser could handle and if it's even feasible. After all, it's not worth waiting days for blood to get cleaned while the virus has had time to spread/repopulate the body with the other blood.

This is (more or less) just some people who do a lot of Raman scattering [wikipedia.org] deciding to try their technique to analyze virus particles and then noticing that some of them were damaged in the process. All of the other stuff (in particular the HIV) is largely BS - a few physicists who know almost nothing about biology going after NIH money by putting the magic "HIV" buzzword into their grant applications.

The slightly cool thing about it is that you can target particles below a certain size (like viruses) without causing much damage to larger particles (like host cells).

In terms of actually engineering this into a system for filtering blood (one of the main applications they envision), there are enough problems that it has no hope of succeeding in practice. Even if you could actually overcome all of those and build a system that could use this technique to destroy all of the virus particles in blood on a practical scale, many viruses that could contaminate whole blood (including HIV) will have uncoated and set up shop in the white cells, which would go on to release new virus after the treatment so this would offer no protection at all.

For the same reason, you couldn't use this as a treatment even if you could somehow expose every cell in a patient to these pulses (which would be impossible unless you cut them into paper-thin slices).

If the Tsens are actually unaware of this, then that alone should raise a huge red flag because anyone with the slightest bit of background in virology would know this.

About the only thing this *might* be good for (other than generating press and bilking naive investors out of their money) is as a laboratory technique for killing all of the free virus in a very small sample without harming the cells.

As a scientist, this kind of thing makes me sick, and it illustrates some of the harm caused by profit-motivated research in university settings (in particular, things Arizona State University's Biodesign Institute [asu.edu]).

It's great when science and discovery naturally leads to practical (and profitable) products, but this kind of thing is what happens when people put the goal of making money ahead of actually doing real science.

Have to agree with this particular AnonCoward. It makes no sense to this biologist either.

Viral, bacterial, or any other genetic material is too similar to the host's when you're talking about mechanical disruption. There's no way to destroy one and not the other.

What's unique about viruses in this context is their coat (capsid) which has a very precise structure. It's different enough from anything else and I could imagine it shattering and nothing else being damaged. If this was somehow (as people have pointed out, that would require magic!) being done in a live person, the immune system would attack the broken particles. Hopefully, it would get them all. If not... see next....

If it was happening in blood filtration, I'd think you'd have to figure out some way of removing the bits and pieces. Virus particles do self-assemble. And evolution being what it is, this would be a good way of selecting for viruses that are particularly good at self-assembling.

As a scientist, I think it's important to distinguish between things we know are possible but can't do, things we don't know if they're possible or not, and things we know are impossible. And there are plenty of things we know are impossible, not just with current technology, but with any technology. Technology can only get you so far, and it's important to understand when fundamental limitations are present. In this case, people are

If this thing eventually leads to cures for HIV and Hepatitis and other nasty viruses, I smell a Nobel Prize for these gentlemen. With corporate sponsorship and help from world governments, AIDS could be eradicated across the globe and improve the quality of life for hundreds of millions of people.

Some of the worst AIDS epidemics are in relatively poor areas where education and prophylactics are in short supply. Defeating a virus is a noble goal, but before that is possible it will be important to work on the problems of feeding and educating at-risk populations. Dying of a nasty disease is nasty. Sentencing people to die of famine by eradicating a nasty disease and causing rapid population growth is cruel.

After reading the article, I'd like to see the actual papers they've written on this. A quick peek at a related link [asu.edu] suggests that the viruses are in water, or within cells in the water. I want to know what happens when you get multiple media interfaces involved, such as within the body, and the degree to which these boundaries will cause a loss in wave "volume" (does Wired mean amplitude?).

My guess is that the experiment involved a very shallow field of activity. The technique as it stands now woul

i'm certain they can tune a laser to the right frequency and shatter a virus like an opera singer and a crystal glasswhat i am also certain of is the fact that a lot of other proteins in the cell probably have the same frequency. some of those proteins might not be so important, some might

if that opera singer went into a lamp store and sang to shatter only the particular crystal chandelier in front of her, no one would be surprised if another chandelier towards the back of the store cracked too

A nice idea. I must be one of the rather few people who have worked with ultrashort pulsed lasers, Raman scattering, and viruses; and I really appreciate the interest of the concept. But I doubt very much that it will ever be a practical tool. Destroying M13 virus in pure water is a far cry from a real application.

If I understand it correctly, the technique exploits the fact that ultrashort laser pulses are not monochromatic but have a significant band width, to excite a vibrational frequency of the virus through resonant Raman excitation. Or, the vibrational mode of the viral capsid is about 8 cm^-1, and the excitation laser contains both 23,529 cm^-1 (i.e. 425 nm) and 23,521 cm^-1 (the Stokes-shifted matching frequency). If you excite the vibrations of the capsid hard enough it will break, as in the old trick of the singer breaking a glass.

But actually, a 100 fs laser pulse has a rather broad spectrum, and therefore is going to excite much more than just that single vibrational mode. Effect on viruses is claimed at a peak power of 50 MW/cm2 -- that is megawatt per square centimeter -- which is rather respectable, even if the average power is low. So I fear that this technique is not going to be very selective. I suppose that in theory you could also excite the virus with two longer-pulse (i.e. picosecond) lasers tuned to have a specific frequency difference, but then the average power required to get a threshold peak power of 50MW/cm2 is likely to be a problem.

Of course, if you are going to use this on a virus like HIV, you will need to target the immature form (which has a shell of gag protein under the envelope) and the mature form (in which gag has been processed into matrix and capsid). You also need to cope with the irregular structure of the virus, which does not have the icosahedral symmetry of many other viruses, its considerable genetic variability, and its variable morphology. HIV capsids occurs in at least two forms, cone-shaped (most of them) and tubular (less frequent). So its Raman frequency spectrum is likely to be complex and a broadband killer may be what you want -- may be.

The reported excitation is a frequency-doubled pulsed beam at 425 nm, which is violet. Blood strongly absorbs light at such wavelengths; hemoglobin even has an absorption peak there. You would have to tune to the red to do anything useful in blood without killing the blood cells, but a standard frequency-doubled titanium-sapphire laser will really struggle to generate red light -- a yellow-tinged green at 550 nm is about the limit. A different laser technology or a much more complex system (with a parametric oscillator) would be required to get there. And even a red laser might be absorbed enough to make blood boil in the focus of the beam.

Last but not least, even if your could destroy all viral particles in a blood sample, that would by no means make that blood safe! The raison d'etre of viruses is inserting their genome into cells to be replicated there. Destroy all viral particles, and there might still be viral genomes in the cells, as RNA or DNA, ready to replicate in the host; even viral proteins ready for assembly into new viruses. It would still be unacceptably dangerous to use that blood.

Frankly, I think this is a misuse of the technology. If it has any applications at all that will be in the study and detection of viruses, not in decontamination. It might be developed into a simpler, cheaper alternative to CARS microscopy.

I agree with what you're saying, and I'd like to add that when you give a person blood, you're really giving them packed red blood cells, which are already "dead," as in they're enucleated cells not actively making new proteins or anything. So you don't need any kind of absolute specificity--it's not like "killing" the blood cells makes them somehow ineffective, so you could probably just gamma-irradiate the blood. I know that's already done under certain circumstances.

There seems to be a lot of people here confused on how this laser can destroy the virus without harming the host cells. Please allow me to explain the natural wonder that is "Natural Harmonic Frequencies".

First, imagine pushing someone on a swing. If you want to make the swing go higher, you have to push it just as it starts to swing forward. That way, the swing's energy is increased by the amount of your push, while still getting the full benefit of it's stored potential energy, and Hey, Presto - the

Nature (if I may anthropomorphize her) has taught us time and time again that she will adapt. Given that this will work, what happens when the virus adapts to 'vibrate' at the same resonance as our cells?

That is, until they install this right on your aorta. Powered by your very own heart, you'll nuke them little bastards during a workout.

Of course... the idea that HIV/AIDS, and or any other STD could be destroyed upon contraction (or, perhaps slowed enough to not make difference) has astounding moral implications. People already lie about the STD's they carry now, but what happens when your guilt could be significantly reduced because, "She/He won't notice until I'm long gone. I guess that makes me a cyn